BACKGROUND: low- and middle-income countries still have a long way to go to reach the fifth Millennium Development Goal of reducing maternal mortality. Mozambique has accomplished a reduction of maternal mortality since the 1990s, but still has among the highest in the world. A key strategy in reducing maternal mortality is to invest in midwifery. AIM: the objective was to explore midwives' perspectives of their working conditions, their professional role, and perceptions of attitudes towards mothers in a low-resource setting. SETTING: midwives in urban, suburban, village and remote areas; working in central, general and rural hospitals as well as health centres and health posts were interviewed in Maputo City, Maputo Province and Gaza Province in Mozambique. METHOD: the study had a qualitative research design. Nine semi-structured interviews and one follow-up interview were conducted and analysed with qualitative content analysis. RESULTS: two main themes were found; commitment/devotion and lack of resources. All informants described empathic care-giving, with deep engagement with the mothers and highly valued working in teams. Lack of resources prevented the midwives from providing care and created frustration and feelings of insufficiency. CONCLUSIONS: the midwives perceptions were that they tried to provide empathic, responsive care on their own within a weak health system which created many difficulties. The great potential the midwives possess of providing quality care must be valued and nurtured for their competency to be used more effectively.

Objective: To determine expression of stanniocalcin-1 (STC1) in human endometrium with and without endometriosis and its regulation by steroid hormones. Design: Laboratory study. Setting: University. Patient(s): Nineteen women with endometriosis and 33 control women. Intervention(s): Endometrial biopsy and fluid sampling. Main Outcome Measure(s): Analysis of early secretory (ESE) and midsecretory (MSE) endometrial secretomes from fertile women with the use of nano-liquid chromatography-dual mass spectrometry;real-time quantitative polymerase chain reaction, and immunohistochemistry for STC1 and its receptor calcium-sensing receptor (CASR) mRNA and proteins in endometrium with and without endometriosis; evaluation of STC1 and CASR mRNA expression in endometrial stromal fibroblasts (eSF) from women with and without endometriosis decidualized with the use of E2P or 8-bromo-cyclic adenosine monophosphate (cAMP). Result(s): STC1 protein was strongly up-regulated in MSE versus ESE in endometrial fluid of fertile women. STC1 mRNA significantly increased in MSE from women with, but not from those without, endometriosis, compared with proliferative endometrium or ESE, with no significant difference throughout the menstrual cycle between groups. STC1 mRNA in eSF from control women increased >230-fold on decidualization with the use of cAMP versus 45-fold from women with endometriosis, which was not seen on decidualization with E-2/P. CASR mRNA did not exhibit significant differences in any condition and was not expressed in isolated eSF. STC1 protein immunoexpression in eSF was significantly lower in women with endometriosis compared with control women. Conclusion(s): STC1 protein is significantly up-regulated in MSE endometrial fluid and is dysregulated in eutopic endometrial tissue from women with endometriosis. It is likely regulated by cAMP and may be involved in the pathogenesis of decidualization defects.

SUMMARY ANSWER: We found no evidence for mutations in NLRP2/7 or KHDC3L in unexplained RPL or infertility.

WHAT IS KNOWN ALREADY: Mutations in NLRP7 and KHDC3L are known to cause biparental hydatidiform moles (BiHMs), a rare form of pregnancy loss. NLRP2, while not associated with the BiHM pathology, is known to cause recurrent Beckwith Weidemann Syndrome (BWS).

STUDY DESIGN, SIZE, AND DURATION: Ninety-four patients with well characterized, unexplained infertility were recruited over a 9-year period from three IVF clinics in Sweden. Blood samples from 24 patients with 3 or more consecutive miscarriages of unknown etiology were provided by the Recurrent Miscarriage Clinic at St Mary's Hospital, London, UK.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients were recruited into both cohorts following extensive clinical studies. Genomic DNA was isolated from peripheral blood and subject to Sanger sequencing of NLRP2, NLRP7 and KHDC3L. Sequence electropherograms were analyzed by Sequencher v5.0 software and variants compared with those observed in the 1000 Genomes, single nucleotide polymorphism database (dbSNP) and HapMap databases. Functional effects of non-synonymous variants were predicted using Polyphen-2 and sorting intolerant from tolerant (SIFT).

MAIN RESULTS AND THE ROLE OF CHANCE: No disease-causing mutations were identified in NLRP2, NLRP7 and KHDC3L in our cohorts of unexplained infertility and RPL.

LIMITATIONS, REASONS FOR CAUTION: Due to the limited patient size, it is difficult to conclude if the low frequency single nucleotide polymorphisms observed in the present study are causative of the phenotype. The design of the present study therefore is only capable of detecting highly penetrant mutations.

WIDER IMPLICATIONS OF THE FINDINGS: The present study supports the hypothesis that mutations in NLRP7 and KHDC3L are specific for the BiHM phenotype and do not play a role in other adverse reproductive outcomes. Furthermore, to date, mutations in NLRP2 have only been associated with the imprinting disorder BWS in offspring and there is no evidence for a role in molar pregnancies, RPL or unexplained infertility.

STUDY FUNDING/COMPETING INTERESTS: This study was funded by the following sources: Estonian Ministry of Education and Research (Grant SF0180044s09), Enterprise Estonia (Grant EU30020); Mentored Resident research project (Department of Obstetrics and Gynecology, Baylor College of Medicine); Imperial NIHR Biomedical Research Centre; Grant Number C06RR029965 from the National Center for Research Resources (NCCR; NIH). No competing interests declared.

Gestational diabetes, obesity, and excessive weight gain are known independent risk factors for the birth of a large for gestational age (LGA) infant. However, only 1 of the 10 infants born LGA is born by mothers with diabetes or obesity. Thus, the aim of the present study was to compare placental gene expression between healthy, nondiabetic mothers (n = 22) giving birth to LGA infants and body mass index-matched mothers (n = 24) giving birth to appropriate for gestational age infants. In the whole gene expression analysis, only 29 genes were found to be differently expressed in LGA placentas. Top upregulated genes included insulin-like growth factor binding protein 1, aminolevulinate synthase 2, and prolactin, whereas top downregulated genes comprised leptin, gametocyte-specific factor 1, and collagen type XVII 1. Two enriched gene networks were identified, namely, (1) lipid metabolism, small molecule biochemistry, and organismal development and (2) cellular development, cellular growth, proliferation, and tumor morphology.

Preeclampsia, especially severe preeclampsia, is associated with an increased risk of cardiovascular disease later in life. However, ultrasound assessments of the common carotid artery intima-media thickness (CCA-IMT) do not convincingly demonstrate this. The aim of this study was to assess whether the individual thickness of the CCA intima and media layers and calculation of intima/media (I/M) ratio indicate an increased cardiovascular risk in women with previous severe PE. The thicknesses of the CCA intima and media layers were obtained by non-invasive high-frequency ultrasound (22 MHz) (Collagenoson, Meudt, Germany) in 42 women with previous severe preeclampsia and 44 women with previous normal pregnancies. A thick intima, thin media and high I/M ratio are signs of a less healthy artery wall. Women with previous severe preeclampsia had a thicker mean CCA intima and a higher I/M ratio than women with previous normal pregnancies (both p < 0.0001). CCA-IMT did not differ significantly between the groups. In receiver operating characteristic (ROC) curve analysis, both intima thickness and I/M ratio clearly discriminated between women with and without previous severe preeclampsia [area under the curve (AUC) about 0.95], whereas CCA-IMT did not (AUC 0.52). Estimation of the individual CCA intima and media layers using high-frequency ultrasound and calculation of the I/M ratio clearly demonstrated the well known increased cardiovascular risk in women with previous severe preeclampsia, whereas CCA-IMT did not. This method appears preferable to measuring CCA-IMT for imaging arterial effects and the increased cardiovascular risk in women with a history of previous severe preeclampsia.

8. Changes in the Artery Wall Layer Dimensions in Women with Preeclampsia

Akhter, Tansim

et al.

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.

Wikström, Anna-Karin

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.

Preeclampsia (PE) is associated with increased risk for cardiovascular disease later in life. Whether, the artery wall layer dimensions differ between PE and normal pregnancy is unclear. The aim of this study was to estimate if women with PE have different common carotid artery wall layer dimensions than women with normal pregnancy, both during pregnancy and about one year postpartum.

Methods:

By using high-frequency (22MHz) ultrasound (Collagenoson, Meudt, Germany) separate estimates of the common carotid artery intima and media layers were obtained and the I/M ratio was calculated in women with PE (n=55 during pregnancy and n=48 at postpartum) and with normal pregnancy (n=65 during pregnancy and n=59 at postpartum). Thick intima, thin media and a high intima/media ratio are signs of less healthy artery wall and vice versa.

Results:

In women with PE, the intima was thicker (0.18 } 0.03 vs. 0.11 } 0.02; p < .001), the media was thinner (0.47 } 0.12 vs. 0.55 } 0.14; p = .001) and the I/M ratio was higher (0.41 } 0.14 vs. 0.20 } 0.05; p < .001) compared to women with normal pregnancy. Further, for changes from pregnancy to postpartum, both for PE and normal pregnancy, the intima and the I/M ratio had improved but still significantly higher in women with PE than in women with normal pregnancy.

Conclusion:

In women with PE, we found a thicker intima, thinner media and a higher I/M ratio compared to women with normal pregnancy, indicating a more negatively affected artery wall layer dimensions. Persisting negative effects of PE on artery wall at postpartum, despite improvement of artery wall layers compared to values during pregnancy, indicates a permanent damage of the vascular system in this group of women.

9. Association between angiogenic factors and signs of arterial aging in women with pre-eclampsia

Akhter, Tansim

et al.

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.

Wikström, Anna-Karin

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Clinical Obstetrics.

Larsson, Marita

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.

OBJECTIVES: Pre-eclampsia (PE) is associated with an increased risk of cardiovascular disease (CVD) later in life. In PE there is a substantial increase in levels of the anti-angiogenic factor soluble fms-like tyrosine kinase-1 (sFlt1) and decreased levels of the pro-angiogenic factor placental growth factor (PlGF). Elevated levels of sFlt1 are also found in individuals with CVD. The aims of this study were to assess sFlt1, PlGF and the sFlt1/PlGF ratio and their correlation with signs of arterial aging by measuring common carotid artery (CCA) intima and media thicknesses and their ratio (I/M ratio) in women with and without PE.

METHODS: Serum sFlt1 and PlGF levels were measured using commercially available enzyme-linked immunosorbent assay kits, and CCA intima and media thicknesses were estimated using high-frequency (22 MHz) ultrasonography in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, with reassessment one year postpartum. A thick intima, thin media and a high I/M ratio indicate a less healthy arterial wall.

RESULTS: During pregnancy, higher levels of sFlt1, lower levels of PlGF and thicker intima, thinner media and higher I/M ratios were found in women with PE vs. controls (all p < 0.0001). Further, sFlt1 and the sFlt1/PlGF ratio were positively correlated with intima thickness and I/M ratio (all p < 0.0001), but negatively correlated with media thickness (p = 0.002 and 0.03, respectively). About one year postpartum, levels of sFlt1 and the sFlt1/PlGF ratio had decreased in both groups, but compared with controls women in the PE group still had higher levels (p = 0.001 and 0.02, respectively). Further, sFlt1 levels and the sFlt1/PlGF ratio were still positively correlated with intima thickness and I/M ratio.

CONCLUSIONS: Higher sFlt1 levels and sFlt1/PlGF ratios in women with PE were positively associated with signs of arterial aging during pregnancy. About one year postpartum sFlt1 levels and the sFlt1/PlGF ratios were still higher in the PE group, and also associated with the degree of arterial aging.

10. Serum Pentraxin 3 is associated with signs of arterial alteration in women with preeclampsia.

Akhter, Tansim

et al.

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Research group (Dept. of women´s and children´s health), Gynecological endocrinology.

BACKGROUND: Preeclampsia (PE) in pregnancy is a state of exaggerated inflammation and is associated with an increased risk of cardiovascular disease (CVD) later in life. Levels of pentraxin 3 (PTX3), a novel inflammation marker, are increased during PE and in individuals with CVD. The primary aim of this study was to assess whether serum PTX3 in women with PE is associated with adverse arterial effects; a thicker intima and higher intima/media (I/M) ratio in the common carotid artery (CCA).

METHODS: Serum PTX3 levels were measured using commercially available enzyme-linked immunosorbent assay kits, and individual CCA intima and media thicknesses were estimated by 22MHz non-invasive ultrasound in 55 women at PE diagnosis and 64 women with normal pregnancies at a similar gestational age, and about one year postpartum. A thick intima, thin media and high I/M ratio indicate a less healthy artery wall.

RESULTS: During pregnancy serum PTX3 correlated positively with intima thickness and I/M ratio but negatively with media thickness (all p<0.0001), indicating adverse arterial effects. About one year postpartum, PTX3 levels had decreased in both groups and there remained no significant group difference or significant correlation with CCA wall layers.

CONCLUSIONS: Higher levels of serum PTX3 in women with PE were significantly associated with signs of adverse arterial effects during pregnancy, but not one year postpartum, supporting the rapid dynamics of PTX3.

11. Symptom Improvement in Social Anxiety Disorder is Associated with Reduced Amygdala Reactivity to Emotional Faces

Alaie, Iman

et al.

Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Frick, Andreas

Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Engman, Jonas

Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Björkstrand, Johannes

Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Faria, Vanda

Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Gingnell, Malin

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Wallenquist, Ulrika

Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Wahlstedt, Kurt

Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Fredrikson, Mats

Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Furmark, Tomas

Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Pediatric reference intervals for thyroid hormones, prolactin and lipids are of high clinical importance as deviations might indicate diseases with serious consequences. In general, previous reference intervals are hampered by the inclusion of only hospital-based populations of children and adolescents. The study included 694 children, evenly distributed from 6 months to 18 years of age. They were recruited as volunteers at child care units and schools. All subjects were apparently healthy and a questionnaire on diseases and medications was filled out by parents and by the older children. TSH, free T4, free T3, total cholesterol, LDL, HDL, triglycerides and prolactin were analyzed on Abbott Architect ci8200. Age- and gender-related 2.5 and 97.5 percentiles were estimated. The thyroid hormone levels were similar to previous data for the Abbott Architect platform, but exhibited differences from studies performed with other methods. Prolactin displayed wide reference ranges, but relatively small age-related changes, and a marginal difference between sexes during adolescence. Reference intervals for lipids in the different age groups are known to vary geographically. Levels of LDL and total cholesterol were higher than those reported for children in Canada, but lower than those reported for children in China. The study gives age-and gender-specific pediatric reference intervals, measured with modern methods for a number of important analytes. The results presented here differ from previously recommended reference intervals. In many earlier studies, retrospective hospital-based reference intervals, which may include various sub-groups have been presented. By non-hospital studies it is possible to avoid some of these biases.

OBJECTIVE: To investigate if topical oxytocin can reverse vaginal atrophy, as assessed by cytological and histological examination of the vaginal mucosal epithelium, in postmenopausal women after 12 weeks of treatment as compared to placebo.

STUDY DESIGN: Sixty-eight postmenopausal women diagnosed with vaginal atrophy were randomized for this multicenter, double-blinded, placebo-controlled trial. Thirty-three women received 600 IU vagitocin, an oxytocin containing gel, and 35 women received a placebo gel intravaginally. The dose was 600 IU daily for the first two weeks and thereafter 600 IU twice a week for 10 weeks. All participant women underwent four visits and a subgroup of 20 women had a further fifth visit. Vaginal smears for cytological evaluation were collected at all visits. Vaginal biopsies were taken in 20 women before and after 12 weeks of treatment for histological analysis. In these women a vaginal smear was also collected after 14 weeks.

RESULTS: The increase in the percentage of superficial cells between 0 and 2 weeks was significantly greater after treatment with vagitocin in comparison with placebo (p = 0.04). The difference in the maturation value between 0 and 12 weeks was significantly higher in the vagitocin than in the placebo group (p = 0.01). The reduction in the scores of atrophy was according to the histological investigation significantly greater in the vagitocin group than in the placebo group at 12 weeks (p < 0.04).

CONCLUSION: Daily intravaginal treatment with vagitocin 600 IU improves expressions of vaginal atrophy as recorded by cytological investigation of vaginal smears and histological analysis of vaginal biopsies. Treatment twice weekly seems to be less effective regarding the increase in superficial cells.

Little consensus has been reached on the best protocol for endometrial preparation for frozen embryo transfer (FET). It is not known how, and to what extent, hormone supplementation in artificial cycles influences endometrial preparation for embryo implantation at a molecular level, especially in patients who have experienced recurrent implantation failure. Transcriptome analysis of 15 endometrial biopsy samples at the time of embryo implantation was used to compare two different endometrial preparation protocols, natural versus artificial cycles, for FET in women who have experienced recurrent implantation failure compared with fertile women. IPA and DAVID were used for functional analyses of differentially expressed genes. The TRANSFAC database was used to identify oestrogen and progesterone response elements upstream of differentially expressed genes. Cluster analysis demonstrated that natural cycles are associated with a better endometrial receptivity transcriptome than artificial cycles. Artificial cycles seemed to have a stronger negative effect on expression of genes and pathways crucial for endometrial receptivity, including ESR2, FSHR, LEP, and several interleukins and matrix metalloproteinases. Significant overrepresentation of oestrogen response elements among the genes with deteriorated expression in artificial cycles (P < 0.001) was found; progesterone response elements predominated in genes with amended expression with artificial cycles (P = 0.0052).

Infant, neonatal and postneonatal mortality and causes of infant death.

RESULTS:

Infant mortality rate was 0.12% (n=2687). Compared with infants born at 40 weeks, risk of infant mortality was increased among early term infants (37 weeks, adjusted OR 1.70, 95% CI 1.43 to 2.02). Compared with infants with normal birth weight for GA, very small for gestational age (SGA; <3rd percentile) infants faced a doubled risk of infant mortality (adjusted OR 2.13, 95% CI 1.80 to 2.53), and corresponding risk was also increased among moderately SGA infants (3rd to <10th percentile; adjusted OR 1.46, 95% CI 1.26 to 1.68). Sudden infant death syndrome (SIDS) was the most common cause of death, accounting for 39% of all infant mortality. Compared with birth at 40 weeks, birth at 37 weeks was associated with increased risks of death by infections, cardiovascular disorders, SIDS and malignant neoplasms. Very and moderately SGA were associated with increased risks of death by neonatal respiratory disorders, infections, cardiovascular disorders, SIDS and neuromuscular disorders. High birth weight for GA was associated with increased risks of death by asphyxia and malignant neoplasms.

CONCLUSION:

Early term birth and very to moderately low birth weight for GA are independent risk factors for infant mortality among non-malformed term infants.

BACKGROUND 'Omics' high-throughput analyses, including genomics, epigenomics, transcriptomics, proteomics and metabolomics, are widely applied in human endometrial studies. Analysis of endometrial transcriptome patterns in physiological and pathophysiological conditions has been to date the most commonly applied 'omics' technique in human endometrium. As the technologies improve, proteomics holds the next big promise for this field. The 'omics' technologies have undoubtedly advanced our knowledge of human endometrium in relation to fertility and different diseases. Nevertheless, the challenges arising from the vast amount of data generated and the broad variation of 'omics' profiling according to different environments and stimuli make it difficult to assess the validity, reproducibility and interpretation of such 'omics' data. With the expansion of 'omics' analyses in the study of the endometrium, there is a growing need to develop guidelines for the design of studies, and the analysis and interpretation of 'omics' data.

METHODS Systematic review of the literature in PubMed, and references from relevant articles were investigated up to March 2013.

RESULTS The current review aims to provide guidelines for future 'omics' studies on human endometrium, together with a summary of the status and trends, promise and shortcomings in the high-throughput technologies. In addition, the approaches presented here can be adapted to other areas of high-throughput 'omics' studies.

CONCLUSION A highly rigorous approach to future studies, based on the guidelines provided here, is a prerequisite for obtaining data on biological systems which can be shared among researchers worldwide and will ultimately be of clinical benefit.

MicroRNAs (miRNAs) act as important epigenetic posttranscriptional regulators of gene expression. We aimed to gain more understanding of the complex gene expression regulation of endometrial receptivity by analyzing miRNA signatures of fertile human endometria. We set up to analyze miRNA signatures of receptive (LH + 7, n = 4) versus prereceptive (LH + 2, n = 5) endometrium from healthy fertile women. We found hsa-miR-30b and hsa-miR-30d to be significantly upregulated, and hsa-miR-494 and hsa-miR-923 to be downregulated in receptive endometrium. Three algorithms (miRanda, PicTar, and TargetScan) were used for target gene prediction. Functional analyses of the targets using Ingenuity Pathways Analysis and The Database for Annotation, Visualization and Integrated Discovery indicated roles in transcription, cell proliferation and apoptosis, and significant involvement in several relevant pathways, such as axon guidance, Wnt/β-catenin, ERK/MAPK, transforming growth factor β (TGF-β), p53 and leukocyte extravasation. Comparison of predicted miRNA target genes and our previous messenger RNA microarray data resulted in a list of 12 genes, including CAST, CFTR, FGFR2, and LIF that could serve as a panel of genes important for endometrial receptivity. In conclusion, we suggest that a subset of miRNAs and their target genes may play important roles in endometrial receptivity.

Background: Improved glycaemic control during pregnancy in mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) has resulted in a marked reduction of perinatal mortality and morbidity, but the prevalence of macrosomia is usually high. Objective: We used non-invasive anthropometric methods to estimate the body composition and the thickness of the interventricular heart septum in 18 infants of mothers with well-controlled T1DM, 10 infants of mothers with GDM and 28 infants of healthy control mothers matched for gestational age and mode of delivery. Methods: Skinfold measurements were obtained with a Harpenden calliper within 48 h after delivery. Echocardiography was also performed to measure the thickness of the interventricular septum. Cord blood was sampled for assays of C-peptide, leptin and IGF-I. Results: The rates of macrosomia (gestational age-adjusted birth weight >2 standard deviation score, SDS) were 56 and 30% in infants of mothers with T1DM and GDM, respectively, compared to 10% in control infants. The body fat content was 40% (0.2 kg) higher and the interventricular heart septum thickness was increased by 20% in both groups of infants of diabetic mothers. We found no associations between maternal levels of HbA1c during pregnancy and body composition or interventricular heart septum thickness. Cord levels of C-peptide and leptin were significantly higher in infants of T1DM mothers than in control infants. Cord leptin level was associated with birth weight SDS and percent body fat in infants of T1DM mothers. IGF-I was associated with percent body fat in infants of GDM mothers and control mothers. A multiple-regression analysis showed that 50% of the variation in body weight SDS could be determined, with IGF-I, leptin and C-peptide as independent variables. Conclusion: Both fat mass and cardiac septal thickness are increased in newborn infants of women with T1DM and GDM in spite of efforts to achieve good glycaemic control during pregnancy.

OBJECTIVE: The aim of the study was to evaluate whether interpreting CTG pairwise brings about a higher level of correctly classified CTG recordings in a non-selected population of midwives and physicians.

STUDY DESIGN: A comparative study.

SETTING: Five delivery units in Stockholm and one delivery unit in Uppsala, with 1589, 3740, 3908, 4539, 6438, and 7331 deliveries in 2011, respectively.

SUBJECTS: 536 midwives and physicians classified one randomly selected CTG recording individually followed by a pairwise classification. The pairs consisted of two midwives (119 pairs) or one midwife and one physician (149 pairs), a total of 268 pairs.

CONCLUSIONS: There was no statistically significant difference when CTG's were classified pairwise compared to individual classifications. The proportion of individually correctly classified CTG's was high (75%). There were differences in the proportion of correctly classified CTG recordings between the delivery units, indicating potential areas of improvement.

Objective. To compare antenatal diagnoses with autopsy findings in pregnancies terminated after ultrasound detection of fetal anomalies. A second aim was to study the quality of antenatal fetal diagnosis over time. Design. Retrospective, multicenter study over two consecutive six-year periods in Uppsala and Stockholm. Setting. Cases were identified through fetal autopsy reports. Subjects. Three hundred and twenty-eight fetuses from pregnancies terminated between 1992 and 2003 because of ultrasonographically diagnosed anomalies. Main outcome measures. The findings at the last ultrasound examination were compared with the autopsy reports. Results. In 299 cases (91.2%) ultrasound findings either exactly matched or were essentially similar to the autopsy findings. In 23 cases (7%) ultrasound findings were not confirmed at autopsy, but the postnatal findings were at least as severe as the antenatal ones. In six cases (1.8%) termination was performed for an anomaly which proved to be less severe than was predicted by ultrasound. The number of such cases was the same in both six-year periods, while the total number of cases increased from 113 in the first to 215 in the second period. Fetal examination provided further diagnostic information in 47% of the cases. In 10% a syndrome was disclosed. Conclusion. Termination of pregnancy was not always based on a correct antenatal diagnosis. All fetuses but one from terminated pregnancies had evident anomalies. In six cases (1.8%) the decision to terminate was based on suboptimal prognostic and diagnostic information. Fetal autopsy by an experienced perinatal pathologist is essential to provide a definitive diagnosis.

Objectives: To evaluate the additional information of second trimester MRI compared to ultrasound in fetuses with identified or suspected non-CNS anomalies and to study the clinical impactof the MRI information on pregnancy management.

Methods: Sixty-three women were included, where the second trimester ultrasound identified or raised suspicion of fetal anomalies. Ultrasound was compared to MRI in relation to the final diagnosis, fetal autopsy if performed or postnatal diagnosis. The additional information of MRI and effect on pregnancy management was estimated in consensus.

Results: The mean gestational age at the last ultrasound before MRI was 18+1 weeks (range 13+0-21+5). The mean interval between ultrasound and MRI was 2.6 days (range 0-15). In 42 (67 %) cases MRI was performed within three days. All MRI examinations were assessable. In 43 (68 %) fetuses MRI provided no additional information, in 17 (27 %) MRI added information without changing the management and in three (5 %) MRI provided additional information which changed the management. These three cases had all oligohydramnios. In all six cases of diaphragmatic hernia MRI provided additional information.

Conclusions: Fetal MRI of non-CNS anomalies is feasible in the second trimester and gives additional information in nearly a third of cases. It may provide a clinically valuable adjunct to ultrasound especially in cases of diaphragmatic hernia or oligohydramnios.

Objective: The aim of this study was to compare women's satisfaction with group based antenatal care and standard care. Design: A randomised control trial where midwives were randomized to perform either GBAC or standard care. Women were invited to evaluate the two models of care. Data was collected by two questionnaires, in early pregnancy and six months after birth. Crude and adjusted odds ratios with a 95% confidence interval were calculated by model of care. Settings: Twelve antenatal clinics in Sweden between September 2008 and December 2010. Participants: Women in various part of Sweden (n = 700). Findings: In total, 8:16 variables in GBAC versus 9:16 in standard care were reported as deficient. Women in GBAC reported significantly less deficiencies with information about labour/birth OR 0.16 (0.10-0.27), breastfeeding OR 0.58 (0.37-0.90) and time following birth OR 0.61 (0.40-0.94). Engagement from the midwives OR 0.44 (0.25-0.78) and being taken seriously OR 0.55 (0.31-0.98) were also found to be less deficient. Women in GBAC reported the highest level of deficiency with information about pregnancy OR 3.45 (2.03-5.85) but reported less deficiency with time to plan the birth OR 0.61 (0.39-0.96). In addition, women in GBAC more satisfied with care in supporting contact with other parents OR 3.86 (2.30-6.46) and felt more support to initiate breastfeeding OR 1.75 (1.02-2.88). Conclusions: Women in both models of care considered the care as deficient in more than half of all areas. Variables that differed between the two models favoured group based antenatal care.

The beneficial effects of tamoxifen in the prevention and treatment of breast cancer are compromised by an increased risk of endometrial polyps, hyperplasia, and cancer. Tamoxifen is metabolized to an array of metabolites with estrogenic effects but also to reactive intermediates that may form protein and DNA adducts. The aim of this study was to investigate cellular [(3)H]tamoxifen adduct formation by light microscopic autoradiography and cell stress by immunohistochemical analysis of glucose-regulating protein 78 (GRP78), nuclear factor kappaB (NF-kappaB), and caspase 3 in human endometrial explants after short-term incubation with tamoxifen. The cellular expression of tamoxifen-metabolizing enzymes in human endometrial biopsy samples was also determined by immunohistochemistry. The results showed selective [(3)H]tamoxifen adduct formation in glandular and surface epithelia after incubation with a nontoxic concentration of [(3)H]tamoxifen (6 nM). There was also a selective expression of the endoplasmic reticulum stress chaperone GRP78 and activated caspase 3 at these sites after incubation with cytotoxic concentrations of tamoxifen (10-100 microM). The cell stress was preferentially observed in samples from women in the proliferative menstrual phase. No treatment-related expression of NF-kappaB was observed. Constitutive expression of the tamoxifen-metabolizing enzymes CYP1B1, CYP2A6, CYP2B6, CYP2C8/9/19, CYP2D6, and SULT2A1 in glandular and surface epithelia was shown, but there was a large interindividual variation. The colocalization of [(3)H]tamoxifen adducts, expression of GRP78, caspase 3, and tamoxifen-metabolizing enzymes in human glandular and surface epithelia suggest a local bioactivation of tamoxifen at these sites and that epithelial cells are early target sites for tamoxifen-induced cell stress.

Human papillomavirus (HPV) 16 is the dominant cofactor in cervical cancer development. The present report investigated the age-specific prevalence of HPV16 in cervical carcinoma in situ (CIS) in females attending organised cervical cancer screening. A retrospective observational study was performed based on individual data from two databases. A total of 162 females aged between 20 and 65 years from Uppsala County, Sweden with CIS and an HPV test conducted between 2010 and 2011, preceding or concomitant to CIS diagnosis, were included. Females with cervical squamous cell carcinoma (SCC; n=35) were used for comparison. In total, 96% (n=156) of females with CIS were positive for high-risk HPV; HPV16 was the most prevalent (44.5%), followed by HPV33/52/58 (19.5%), HPV31 (13.1%) and HPV18145 (9.5%). HPV16 was most frequently detected in females with CIS aged between 20 and 29 years (73.6%) and least frequently detected in those aged between 50 and 65 years (33.3%), with a statistically significant age-specific difference (P=0.001). Among the HPV16-positive females, multiple infections were most frequent in the younger age groups. The prevalence of HPV16 in females with CIS decreased with age, whereas a high prevalence of HPV16 remained in females with SCC. These results may indicate that HPV16 has increased oncogenic potential in older females.

The incidence rates of cervical adenocarcinoma have been increasing over the last two decades, contrary to those of squamous cell carcinoma. This trend is particularly evident among females aged <40 years and has occurred despite extensive cytology-based screening programs. The aim of the present retrospective database study was to investigate adenocarcinoma in situ (AIS) with respect to previous cytological results, high-risk (HR) human papillomavirus (HPV) infections and histological results from AIS-adjacent squamous mucosa. Databases were used to identify 32 female patients with AIS treated for various conditions between 2009 and 2012 at the Department of Gynecology, Uppsala University Hospital (Uppsala, Sweden) and previous cytological, HPV and histological results. Of the individuals in the study, 64.3% had a previously recorded cytological result showing squamous cell abnormalities; five had glandular cell abnormalities (18%) and two had AIS (7.1%). Among the patients with available HPV results, 95% were HR-HPV-positive; HPV18/45 predominated (77%), followed by HPV16 (27%). The patients with multiple HPV infections were aged <= 32 years, while patients aged >= 38 years were only infected with HPV18/45. All but three patients had cervical intraepithelial neoplasia (CIN) in the AIS-adjacent squamous mucosa, 79% of which was CIN2 or worse. The present retrospective database study suggests that AIS is detected at screening mainly due to simultaneous squamous precursor lesions and that HPV18/45 infection is an increasing co-factor for AIS in older patients. HPV analyses of glandular precursor lesions aid in the identification of female individuals at risk of progression to invasive disease, and thus have a favorable effect on adenocarcinoma prevention, together with vaccination.

Deregulation of emergency contraceptive pills (ECP) has led to pharmacy staff becoming a new provider group of ECP, together with nurse-midwives, who are already experienced in prescribing contraceptives. This postal questionnaire survey aimed to assess practices and attitudes towards ECP and the over-the-counter (OTC)-availability among pharmacy staff (n=237) and nurse-midwives (n=163). The overall response rate was 89%. Both study groups were positive to ECP and the OTC-availability and the vast majority agreed that sexually active women should be aware of ECP and that routine information about ECP should be included in contraceptive counseling. Verbal information on all aspects of ECP to clients was reported more often by nurse-midwives than by pharmacy staff. Both groups supported collaboration between providers. Our findings suggest that further collaboration between pharmacies and family planning clinics should be encouraged to ensure a competent and client-friendly provision of ECP.

Objective: To investigate primiparous women's preferences for care during a prolonged latent phase of labour. Methods: A qualitative study based on focus groups and individual interviews and analysed with inductive content analysis. Results: Sixteen primiparous women with a prolonged latent phase of labour >18 hours were interviewed in five focus groups (n = 11) or individually (n = 5). One main category emerged "Beyond normality - a need of individual adapted guidance in order to understand and manage an extended latent phase of labour" which covers the women's preferences during the prolonged latent phase. Five categories were generated from the data: "A welcoming manner and not being rejected", "Individually adapted care", "Important information which prepares for reality and coping", "Participation and need for feedback" and "Staying nearby the labour ward or being admitted for midwifery support". Women with a prolonged latent phase of labour sought to use their own resources, but their needs for professional support increased as time passed. A welcoming attitude from an available midwife during the latent phase created a feeling of security, and personally adapted care was perceived positively. Conclusions: Women with a prolonged latent phase of labour preferred woman-centred care. Midwives play an important role in supporting these women. Women's need for midwifery-support increases as the time spent in latent phase increases.

Background. Hysterectomies are very common, and most of them are still performed abdominally. The minimally invasive alternatives are perceived as difficult by gynecologists. Robotic assistance is thought to facilitate laparoscopic surgery. The aim of this study was to compare the surgical outcomes of robotic-assisted and conventional total laparoscopic hysterectomy. Methods. Patients, candidate to hysterectomy for benign indications, were allocated to either robotic or conventional laparoscopy in a quasi-randomized fashion. Patients were operated following a standardized surgical protocol. Main outcome measures were total surgical time, conversions to laparotomy, blood loss, hospital stay, and complications. Results. Fifty-one patients underwent robotic hysterectomy (mean age = 46.59 years) and 54 conventional laparoscopy (mean age = 50.02 years). The groups were homogeneous in body mass index and uterine weight. Robotic-assisted hysterectomies were significantly shorter (154.63 +/- 36.57 vs 185.65 +/- 42.98 minutes in the control group; P =.0001). Patients in the robotic group also had a significantly smaller reduction in hemoglobin (9.69% +/- 8.88% vs 15.29% +/- 8.39% in controls; P =.0012) and hematocrit (10.56% +/- 8.3% vs 14.89% +/- 8.11%; P =.008). No intraoperative conversions to laparotomy were required. Complication rate was low and similar in both groups. All patients were fully recovered at 1-month follow-up outpatient visit. Conclusions. Significantly lower operative times and blood loss indicate that robotic assistance can facilitate surgery already during the learning curve period. Nevertheless, proficiency can be reached in conventional laparoscopy through training, and the cost-effectiveness of robotic hysterectomy for benign conditions is yet to be confirmed.

Background: Birth preparedness and complication readiness (BP/CR) strategies are aimed at reducing delays in seeking, reaching, and receiving care. Counselling on birth preparedness is provided during antenatal care visits. However, it is not clear why birth preparedness messages do not translate to utilisation of facility delivery. This study explores the perceptions, experiences, and challenges the community faces on BP/CR. Design: A qualitative study design using Focused Group Discussions was conducted. Twelve focus group discussions were held with four separate groups: young men and women and older men and women in a rural community in Tanzania. Qualitative content analysis was used to analyse the data. Results: The community members expressed a perceived need to prepare for childbirth. They were aware of the importance to attend the antenatal clinics, relied on family support for practical and financial preparations such as saving money for costs related to delivery, moving closer to the nearest hospital, and also to use traditional herbs, in favour of a positive outcome. Community recognised that pregnancy and childbirth complications are preferably treated at hospital. Facility delivery was preferred; however, certain factors including stigma on unmarried women and transportation were identified as hindering birth preparedness and hence utilisation of skilled care. Challenges were related to the consequences of poverty, though the maternal health care should be free, they perceived difficulties due to informal user fees. Conclusions: This study revealed community perceptions that were in favour of using skilled care in BP/CR. However, issues related to inability to prepare in advance hinder the realisation of the intention to use skilled care. It is important to innovate how the community reinforces BP/CR, such as using insurance schemes, using community health funds, and providing information on other birth preparedness messages via community health workers.

Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.

To examine associations between antenatal exposure to Swedish oral moist snuff (which includes essentially only nicotine) and to smoking and risks of small-for-gestational-age (SGA) births and to compare risks among women who stopped or continued using snuff or smoking during pregnancy.

SGA birth, also stratified into preterm (≤36 weeks of gestation) and term (≥37 weeks of gestation) SGA births.

RESULTS:

Compared with non-tobacco users in early pregnancy, snuff users and above all smokers in early pregnancy had increased risks of SGA births: adjusted ORs (95% CI) were 1.26 (1.09-1.46) and 2.55 (2.43-2.67), respectively). Snuff use had, if anything, a stronger association with preterm SGA than term SGA, whereas the opposite was true for smoking. Compared with non-tobacco users, women who stopped using snuff before their first visit to antenatal care had no increased risks of preterm or term SGA, and women who stopped using snuff later during pregnancy had no increased risk of term SGA. Smoking cessation early in pregnancy was associated with a larger reduction in risk than smoking cessation later in pregnancy.

CONCLUSIONS:

As both smoking and snuff use influence risk of SGA, both nicotine but above all tobacco combustion products are involved in the mechanisms by which maternal smoking increases the risk of SGA.

The mechanisms by which antenatal smoking exposure increases the risk of preterm birth remain unknown. Swedish oral moist snuff contains quantities of nicotine comparable to those typically absorbed from cigarette smoking, but does not result in exposure to the products of combustion, for example carbon monoxide. In a nationwide study of 776,836 live singleton births in Sweden from 1999 to 2009, the authors used multiple logistic regression models to examine associations between cessation of smoking and Swedish snuff use early in pregnancy and risk of preterm birth (before 37 weeks). Compared with nontobacco users both before and in early pregnancy, the adjusted odds ratios (OR), 95 % confidence interval (CI) were OR = 0.92, 95 % CI 0.84-1.01, for women who stopped using snuff, and OR = 0.90, 95 % CI 0.87-0.94, for women who stopped smoking. In contrast, continued snuff use and smoking were associated with increased risks of preterm birth (adjusted OR = 1.29, 95 % CI 1.17-1.43, adjusted OR = 1.30, 95 % CI 1.25-1.36, respectively). The snuff and smoking-related risks were, if anything, higher for very (before 32 weeks) than moderately (32-36 weeks) preterm birth, and also higher for spontaneous than induced pretermbirth. These findings suggest that antenatal exposure to nicotine is involved in the mechanism by which tobacco use increase the risk of preterm birth.

Prenatal exposure to Swedish snuff (including nicotine and other components in grinded tobacco) is reported to increase stillbirth risk, but the effect of snuff on early neonatal mortality is unknown. Prenatal smoking exposure is associated with risks for both stillbirth and early neonatal mortality. We aimed to study if women who quit using snuff or quit smoking before first antenatal visit reduce their risks. In a nationwide study of 851,371 singleton births in Sweden from 1999 to 2010, we used multiple logistic regression models to examine associations between cessation or continuation of snuff use or smoking and risks for stillbirth (at 28 weeks or later) and early neonatal mortality (death during the first week of life). Compared with nontobacco users, snuff users and smokers in early pregnancy had increased risks for stillbirths, and adjusted odds ratios (ORs), with 95% confidence intervals (CI), were 1.43 (1.021.99) and 1.59 (1.401.80), respectively. Women who stopped using snuff or stopped smoking before first visit to antenatal care had no increased risks. Compared with nontobacco users, smokers had an increased risk for early neonatal mortality (adjusted OR 1.37 [95% CI 1.111.71]). Women who stopped smoking and snuff users in early pregnancy had no increased risks of early neonatal mortality. Both snuff and smoking influence risk for stillbirth, and women who stop using snuff or smoking have a similar stillbirth risk as nontobacco users. Smoking but not snuff use influences risk for early neonatal mortality.

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.

Gingnell, Malin

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Engman, Jonas

Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Premenstrual dysphoric disorder (PMDD) has generally not been associated with impulsive behavior. However, some studies suggest that women with PMDD have higher impulsivity scores than healthy controls and that brain activity during response inhibition may vary across the menstrual cycle. Therefore, our aim was to unravel potentially important cognitive aspects of PMDD by investigating brain activity during response inhibition in women with PMDD and healthy controls in relation to menstrual cycle phase.

METHODS:

Fourteen PMDD patients and 13 healthy controls performed a Go/NoGo task to measure brain activity during response inhibition by use of event-related functional magnetic resonance imaging.

RESULTS:

Women with PMDD displayed decreased activity during both menstrual cycle phases compared to healthy controls in several task-related parietal areas. A significant group by phase interactions was found in the left insula, driven by enhanced activity among healthy controls in the follicular phase and by enhanced insula activity during the luteal phase among PMDD patients.

LIMITATIONS:

The limitations of the present study are the relatively limited sample size, the relatively small number of NoGo trials and the lack of a baseline contrast for the NoGo trials.

CONCLUSIONS:

During response inhibition women with PMDD have reduced activity in areas associated with attention and motor function which is unrelated to menstrual cycle phase. Insular cortex activity, involved in both affective and cognitive processing, was significantly activated during the luteal phase among PMDD women. These findings are relevant for the understanding of how ovarian steroids influence mood symptoms in women.

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

Engman, Jonas

Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

The postpartum period is characterized by complex hormonal changes, but human imaging studies in the postpartum period have thus far predominantly focused on the neural correlates of maternal behavior or postpartum depression, whereas longitudinal studies on neural correlates of cognitive function across the postpartum period in healthy women are lacking. The aim of this study was to longitudinally examine response inhibition, as a measure of executive function, and its neural correlates in healthy postpartum women and non-postpartum controls. Thirteen healthy postpartum women underwent event-related functional magnetic resonance imaging while performing a Go/NoGo task. The first assessment was made within 48hours of delivery, and the second at 4-7 weeks postpartum. In addition, 13 healthy women examined twice during the menstrual cycle were included as non-postpartum controls. In postpartum women region of interest analyses revealed task-related decreased activations in the right inferior frontal gyrus, right anterior cingulate, and bilateral precentral gyri at the late postpartum assessment. Generally, postpartum women displayed lower activity during response inhibition in the bilateral inferior frontal gyri and precentral gyri compared to non-postpartum controls. No differences in response inhibition performance were found between time-points or between groups. In conclusion, this study has discovered that brain activity in prefrontal areas during a response inhibition task decreases throughout the course of the first postpartum weeks and is lower than in non-postpartum controls. Further studies on the normal adaptive brain activity changes that occur during the postpartum period are warranted.

Aromatase inhibitor users did not differ in dihydrotestosterone, total testosterone, androstenedione, DHEA, or free androgen index levels from healthy controls or untreated breast cancer patients. The highest total testosterone levels were found in tamoxifen-treated women, who had significantly higher plasma concentrations than both women treated with aromatase inhibitors and breast cancer patients without adjuvant treatment. Concentrations of cortisol and cortisone were significantly greater in aromatase inhibitor users as well as tamoxifen users, in comparison with healthy controls and untreated breast cancer patients. Aromatase inhibitor users had lower estrone and estradiol plasma concentrations than all other groups.

Conclusion

Adjuvant treatment with aromatase inhibitors or tamoxifen was associated with increased cortisol and cortisone plasma concentrations as well as decreased estradiol concentrations. Androgen levels were elevated in tamoxifen-treated women but not in aromatase inhibitor users.

The goal of this study was to investigate sexual function in postmenopausal breast cancer patients treated with aromatase inhibitors.

METHODS:

A population-based, cross-sectional study was conducted among postmenopausal breast cancer patients on adjuvant endocrine treatment and age-matched controls with and without estrogen treatment. Sexual function was assessed with a standardized questionnaire.

RESULTS:

In all, 42.4% of aromatase inhibitor-treated breast cancer patients were dissatisfied with their sex life in general, and 50.0% reported low sexual interest; this was significantly more common than in tamoxifen-treated patients and controls (P < 0.05). Aromatase inhibitor-treated patients reported insufficient lubrication in 73.9% and dyspareunia in 56.5% of cases, which were significantly more common than in controls, irrespective of hormonal use (P < 0.05). Tamoxifen-treated patients reported significantly more dyspareunia (31.3%; P < 0.05) but resembled controls in all other concerns.

Early parental bonding with preterm babies is particularly important, and the aim of our study was to explore when parents experienced what they regarded as important events for the first time while their infant was in the neonatal intensive care unit (NICU).

METHODS:

The study was part of a longitudinal project on Kangaroo Mother Care at two Swedish university hospitals. The parents of 81 infants completed questionnaires during their infants' hospital stay.

RESULTS:

Most parents saw and touched their infants immediately after birth, but only a few could hold them skin to skin or swaddle them. Other important events identified by parents included the first time they performed care giving activities and did so independently, interaction and closeness with the infant, signs of the infant's recovery and integration into the family. The timing of the events depended on the physical design of the NICU, whether parents' could stay with their infant round-the-clock and when they were allowed to provide care under supervision and on their own.

CONCLUSION:

The design and routines of the NICU dictated when parents first interacted with their infants. Clinical guidelines that facilitate early contact with preterm babies can help parents to make the transition to their parental role.

The study objective was to improve ultrasonic diagnosis of retained placental tissue by measuring the volume of the uterine body and cavity using three-dimensional (3D) ultrasound. Twenty-five women who were to undergo surgical curettage due to suspected retained placental tissue were included. The volume of the uterine body and cavity was measured using the VOCAL imaging program. Twenty-one women had retained placental tissue histologically verified. Three of these had uterine volumes exceeding the largest volume observed in the normal puerperium. Seventeen of the 21 women had a uterine cavity volume exceeding the largest volume observed in the normal puerperium. In all 14 cases examined 28 days or more after delivery the cavity volume exceeded the largest volume observed in the normal puerperium. A large cavity volume estimated with 3D ultrasound is indicative of retained placental tissue. However, 3D ultrasound adds little or no diagnostic power compared to 2D ultrasound.

Fifty women with uncomplicated deliveries and puerperium between February 2009 and February 2010.

Methods.

Three-dimensional ultrasound was used to measure the uterine body and cavity volumes. The volume data set was analysed using virtual organ computer-aided analysis (VOCAL) with a 30 degree rotation step. Measurements were performed transabdominally on days 1, 7 and 14 and transvaginally on days 28 and 56 postpartum. Parity, gestational age, birthweight, smoking, breastfeeding and blood loss were recorded.

Main outcome measures.

Uterine body and cavity volumes. Results. Median uterine body volume was 756 cm3 on day 1, 440 cm3 on day 7, 253 cm3 on day 14, 125 cm3 on day 28 and 68 cm3 on day 56. Median cavity volume was 22 cm3 on day 1, 18 cm3 on day 7, 6 cm3 on day 14, 1 cm3 on day 28 and not measurable on day 56. The interindividual variation of uterine body and cavity volumes was most pronounced on day 1 and decreased throughout the observation period. Intrauterine content was found in 36% of the women on day 1, 95% on day 7, 87% on day 14 and 28% on day 28.

Conclusions.

Three-dimensional ultrasound is a non-invasive tool suitable for measurement of the uterine body and cavity volumes during the puerperium. The volumes decreased in a similar pattern in the study population.

OBJECTIVE: To evaluate whether women with a caesarean section at their first delivery have an increased risk of retained placenta at their second delivery.

DESIGN: Population-based cohort study.

SETTING: Sweden.

POPULATION: All women with their first and second singleton deliveries in Sweden during the years 1994-2006 (n = 258 608). Women with caesarean section or placental abruption in their second pregnancy were not included in the study population.

METHODS: The risk of retained placenta at second delivery was estimated for women with a first delivery by caesarean section (n = 19 458), using women with a first vaginal delivery as reference (n = 239 150). Risks were calculated as odds ratios by unconditional logistic regression analysis with 95% confidence intervals (95%) after adjustments for maternal, delivery, and infant characteristics.

RESULTS: The overall rate of retained placenta was 2.07%. In women with a previous caesarean section and in women with previous vaginal delivery, the corresponding rates were 3.44% and 1.96%, respectively. Compared with women with a previous vaginal delivery, women with a previous caesarean section had an increased risk of retained placenta (adjusted OR 1.45; 95% CI 1.32-1.59), and the association was more pronounced for retained placenta with heavy bleeding (adjusted OR 1.61; 95% CI 1.44-1.79).

CONCLUSIONS: Our report shows an increased risk for retained placenta in women previously delivered by caesarean section, a finding that should be considered in discussions of mode of delivery.

Objective. To assess the current knowledge concerning progestogen-only contraception (POC) and risks of venous thromboembolism (VTE). Design and setting. Systematic review of the literature on observational and analytical studies reporting risk estimates for VTE in women exposed to POCs. Methods and main outcome measures. We performed a computerized literature search in the Pub Med, Embase, and the Cochrane Library for studies published between 1966 and February 13, 2008. Based on the evaluated studies we calculated an overall risk estimate for VTE in association with POC. Results. Four case-control studies and one cohort study were included. Of the case-control studies, three reported an increased risk and one a decreased risk of VTE. The cohort study found divergent results depending on the type of statistical analysis used. None of the results was statistically significant. The overall odds ratio for POC-associated VTE in the four case-control studies was 1.45 (95% CI=0.92-2.26). Conclusions. The risk of VTE associated with use of POCs is poorly investigated. The slightly elevated overall risk estimate might suggest an association between POC and an increased risk for VTE. The results must, however, be interpreted with caution due to the possibility of residual confounding. Well-designed studies with sufficient statistical power to evaluate risks of VTE with POC are warranted.

A case-control study was performed to evaluate the Swedish population-based symphysis fundus (SF) reference curves. The study included 242 small for gestational age (SGA) neonates (169 term and 73 preterm infants) as cases and 296 non-SGA infants as controls. Two Swedish SF curves were evaluated. In term pregnancies they showed a sensitivity of 32 % and 51 % and a specificity of 90 % and 83 %, respectively, at a cut-off level of < - 2 SD from the mean according to the SF reference curve. The sensitivity for SGA was higher in preterm pregnancies (49 % and 58 %, respectively) and the first alarm below – 2 SD was noted before 32 weeks in 37 % and 43 % of the preterm pregnancies, respectively. (Study I)

A study of self-administered SF measurements was designed to achieve more regular and frequent SF measurements. Thirty-three women with singleton, ultrasound dated pregnancies performed SF measurements on average 14 weeks from gestational week 20 to 25 until delivery. Self-administered SF measurements were higher and had higher variance than midwives’ measurements. Four consecutive SF measurements on each occasion can compensate for higher variance. Reliable self-administered SF measurements can be obtained. (Study II)

Self-administered SF measurements from 191 women were used to construct absolute and relative SF growth references. The influence of fetal sex, maternal obesity and parity was assessed in regression models. The lnSF growth was statistically influenced by maternal obesity, and a borderline significance was recorded for fetal sex and parity. Statistical analysis and graphical displays show no evidence that the relative lnSF growth should be dependent on these variables. (Study III)

To improve detection of infants with intrauterine growth restriction (IUGR) rather than SGA a new statistical model (the SR method) was used. The SR method was evaluated with SF measurements from 1122 pregnant women. The sensitivity for neonatal morbidity and SGA was low, between 6 and 36 % for SGA (< -2SD). Neonates classified as SGA (< -2SD and < 10th percentile) had increased morbidity compared with the total study group. Neonates suspected to be SGA before delivery by the population-based SF measurement method had lower morbidity than those not suspected. The SR method was found not to improve detection of fetuses with increased morbidity or SGA neonates in this study. Better screening methods to detect IUGR and SGA prior to delivery are needed. (Study IV)

Objective: The statistical method of Shiryaev-Roberts (SR method), using altered growth speed, in combination with symphysis fundus (SF) measurements has theoretically a potential to improve antenatal detection of intrauterine growth restricted (IUGR) fetuses. The main objective of the present study was to compare the ability of the SR method and the SF method (SF measurements compared with a population based reference curve) to identify IUGR and small for gestational age (SGA) fetuses.

Methods: Weekly self-administered SF measurements from gestational week 25 until delivery were analysed according to the SR method. Neonatal morbidity was used as a proxy for IUGR. SGA was defined as a birth weight < -2 standard deviations (SD) or < 10th percentile. Sensitivity for neonatal morbidity and SGA were assessed for alarms given for 5 to 30 % of the study population according to the SR-method and compared with the SF method.

Results: SF measurements from 1122 pregnant women were evaluated. For the SR method sensitivity for neonatal morbidity was between 6.0 and 36.4 %, for SGA (< -2 SD) 36.8 %, and for SGA (< 10th percentile) 20.9 %. The SF method had a sensitivity between 6.0 and 13.8% for neonatal morbidity, for SGA (< -2 SD) 52.3 % and for SGA (< 10th percentile) 28.6 %. Neonates classified as SGA (< -2SD and < 10th percentile) had increased morbidity. Neonates suspected to be SGA before delivery by the SF method had lower morbidity than those not suspected.

Conclusions: The SR method was not found to improve detection of fetuses with increased morbidity or SGA neonates in this study. SGA neonates defined as < – 2 SD or < 10th percentile have increased neonatal morbidity.

48. Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects

Bergman, Lina

et al.

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.

Akhter, Tansim

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.

Wikström, Anna-Karin

Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.

S100B is supposed to be a peripheral biomarker of central nervous system (CNS) injury. The purpose of this study was to compare levels of S100B in women with preeclampsia with levels in healthy pregnant control subjects and furthermore to analyze levels of S100B in relation to possible CNS effects.

METHODS:

A cross-sectional case-control study in antenatal care centers in Uppsala, Sweden, was performed. Fifty-three women with preeclampsia and 58 healthy pregnant women were recruited at similar gestational length; women with preeclampsia were recruited at time of diagnosis, and control subjects were recruited during their routine visit to an antenatal clinic. Plasma samples were collected, and levels of S100B were analyzed with an enzyme-linked immunosorbent assay. Information about demographic and clinical characteristics, including symptoms related to CNS affection, was collected from the medical records. The main outcome measures were plasma levels of S100B and possible CNS effects.

RESULTS:

Levels of S100B were significantly higher among women with preeclampsia than among control subjects (0.12 µg/L vs. 0.07 µg/L; P < 0.001). In preeclampsia, there was a significant association between high levels of S100B and visual disturbances (P < 0.05).

CONCLUSIONS:

S100B is increased among women with preeclampsia, and high levels of S100B associate with visual disturbances, which might reflect CNS affection in women with preeclampsia.

Objectives: Neuron-specific enolase (NSE) is considered to be a peripheral biomarker of central nervous system injury. The aim of this study was to compare levels of NSE throughout pregnancy, in healthy pregnant women and in women developing preeclampsia. Methods: A nested case-control study within a longitudinal study cohort was performed. Four hundred sixty nine healthy pregnant women were enrolled, and plasma samples were collected at gestational weeks 10, 25, 28, 33, and 37. Levels of NSE were analyzed in 16 women with preeclampsia and 36 controls throughout pregnancy with an enzyme-linked immunosorbent assay. Results: In gestational week 37, women who developed preeclampsia had significantly higher plasma levels of NSE than healthy pregnant controls (P < .001). The levels of NSE did not change between gestational weeks 10 and 37 in women who developed preeclampsia, but the levels decreased significantly in healthy pregnant controls (P < .001). Conclusion: In pregnant women developing preeclampsia, the levels of NSE remained high throughout pregnancy, whereas in healthy women, these tended to decline over time, especially at the 2 last time points. The result might be confounded in early pregnancy by extracerebral sources of NSE, such as the corpus luteum. Findings need to be confirmed in a larger prospective study.